Impact of Technique and Schedule of Reirradiation Plus Hyperthermia on Outcome after Surgery for Patients with Recurrent Breast Cancer.

PURPOSE: Combining reirradiation (reRT) with hyperthermia (HT) has shown to be of high therapeutic value for patients with loco-regionally recurrent breast cancer. The purpose of this study was to compare the long-term therapeutic effect and toxicity of reRT + HT following surgery of loco-regionally recurrent breast cancer using two different reRT regimens. METHODS: The reRT regimen of the 78 patients treated in Institute A consisted of 8 × 4 Gy twice a week using mostly abutted photon-electron fields. The 78 patients treated in Institute B received a reRT regimen of 12 × 3 Gy, four times a week with single or multiple electron fields. Superficial hyperthermia was applied once a week in Institute A and twice a week in Institute B. Both institutes started HT treatment within 1 hour after reRT and used the same 434-MHz systems to heat the tumor area to 41-43 °C. RESULTS: The 5-year-infield local control (LC) rates were similar; however, the 5-year-survival rates were 13% lower in Institute A. Most remarkable was the difference in risk with respect to 5-year ≥ grade 3 toxicity, which was more than twice as high in Institute A. CONCLUSION: The combination of reirradiation and hyperthermia after macroscopically complete excision of loco-regional breast cancer recurrences provides durable local control in patients at risk for locoregional recurrent breast cancer. Treatment is well tolerated with the 12 × 3 Gy schedule with limited-sized electron fields.

Reirradiation + hyperthermia for recurrent breast cancer en cuirasse.

BACKGROUND AND PURPOSE: Patients with irresectable locoregional recurrent breast cancer en cuirasse (BCEC) do not have effective curative treatment options. Hyperthermia, the elevation of tumor temperature to 40-45 °C, is a well-established radio- and chemotherapy sensitizer. A total of 196 patients were treated with reirradiation and hyperthermia (reRT+HT) at two Dutch institutes from 1982-2005. The palliative effect was evaluated in terms of clinical outcome and toxicity. PATIENTS AND METHODS: All patients received previous irradiation to a median dose of 50 Gy. In all, 75% of patients received 1-6 treatment modalities for previous tumor recurrences. ReRT consisted of 8 × 4 Gy given twice a week or 12 × 3 Gy given four times a week. Superficial hyperthermia was added once or twice a week. Tumor area comprised ≥½ of the ipsilateral chest wall. RESULTS: Overall clinical response rate was 72% (complete response [CR] 30%, partial response [PR] 42%, stable disease [SD] 22%, progressive disease [PD] 6%). The local progression-free rate at 1 year was 24%. Median survival was 6.9 months. Forty-three percent of our patients with CR, PR, SD after treatment remained infield progression-free until death or last follow-up. Acute ≥grade 3 toxicity occurred in 33% of patients, while late ≥grade 3 toxicity was recorded in 14% of patients. Tumor ulceration prior to treatment had a negative impact on both clinical outcome and toxicity. CONCLUSION: ReRT+HT provides sustainable palliative tumor control, despite refractory, extensive tumor growth. Compared to currently available systemic treatment options, reRT+HT is more effective with less toxicity.

A flexible 70 MHz phase-controlled double waveguide system for hyperthermia treatment of superficial tumours with deep infiltration.

PURPOSE: Superficial tumours with deep infiltration in the upper 15 cm of the trunk cannot be treated adequately with existing hyperthermia systems. The aim of this study was to develop, characterise and evaluate a new flexible two-channel hyperthermia system (AMC-2) for tumours in this region. MATERIALS AND METHODS: The two-channel AMC-2 system has two horizontally revolving and height adjustable 70 MHz waveguides. Three different interchangeable antennas with sizes 20 × 34, 15 × 34 and 8.5 × 34 cm were developed and their electrical properties were determined. The performance of the AMC-2 system was tested by measurements of the electric field distribution in a saline water filled elliptical phantom, using an electric field vector probe. Clinical feasibility was demonstrated by treatment of a melanoma in the axillary region. RESULTS: Phantom measurements showed a good performance for all waveguides. The large reflection of the smallest antenna has to be compensated by increased forward power. Field patterns become asymmetrical when using smaller top antennas, necessitating phase corrections. The clinical application showed that tumours deeper than 4 cm can be heated adequately. A median tumour temperature of 42 °C can be reached up to 12 cm depth with adequate antenna positioning and phase-amplitude steering. CONCLUSIONS: This 70 MHz AMC-2 waveguide system is a useful addition to existing loco-regional hyperthermia equipment as it is capable of heating axillary tumours and other tumours deeper than 4 cm.

Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer: Predictive factors.

BACKGROUND: Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. PATIENTS AND METHODS: From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. RESULTS: The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000. DISCUSSION AND CONCLUSION: ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures.

Reirradiation and hyperthermia for irresectable locoregional recurrent breast cancer in previously irradiated area: Size matters.

BACKGROUND/PURPOSE: Treatment options for irresectable locoregional recurrent breast cancer in previously irradiated area are limited. Hyperthermia, elevating tumor temperature to 40-45°C, sensitizes radio-and-chemotherapy. Four hundred and fourteen patients treated with reirradiation+hyperthermia (reRT+HT) in the AMC(n=301) and the BVI(n=113), from 1982 to 2005 were retrospectively analyzed for treatment response, locoregional control (LC) and prognostic factors for LC and toxicity. PATIENTS/METHODS: All patients received previous irradiation (median 50 Gy). reRT consisted of 8 × 4 Gy-2/week (AMC) or 12 × 3 Gy-4/week (BVI). Hyperthermia was added once (AMC)/twice (BVI) a week. RESULTS: Overall clinical response rate was 86%. The 3-year LC rate was 25%. The number of recurrence episodes, distant metastases (DM), tumor site, tumor size, time to recurrence and treatment year were significant for LC. Acute ⩾ grade 3 toxicity occurred in 24% of patients. Actuarial late ⩾ grade 3 toxicity was 23% at 3-years. In multivariable analysis reRT fraction dose was significantly related to late ⩾ grade 3 toxicity. CONCLUSION: reRT+HT is an effective curative and palliative treatment option for patients with irresectable locoregional recurrent breast cancer in previously irradiated area. Early referral, treatment of chest wall recurrences ⩽ 5 cm in the absence of distant metastases, provided the highest local control rates. The cumulative effects of past and present treatments should be accounted for by adjusting treatment protocol to minimize toxicity.

Reirradiation and hyperthermia for radiation-associated sarcoma.

BACKGROUND: The objective of this study was to evaluate the role of reirradiation and hyperthermia in the treatment of radiation-associated sarcoma (RAS) in the thoracic region, which is an increasing, yet extremely rare condition with a poor prognosis. METHODS: Between 1979 and 2009, 16 patients with RAS in the thoracic region were treated in the Academic Medical Center and the Institute Verbeeten with reirradiation and hyperthermia. In 13 patients, this treatment was given for unresectable disease and 3 times after resection as adjuvant treatment. The median latency period between the original malignancy diagnosis and the RAS diagnosis was 86 months (range 19-212 months). Histology was angiosarcoma in 11 patients (69%). The literature on reirradiation with or without hyperthermia for RAS was reviewed. RESULTS: The median survival was 15.5 months (range, 3-204 months). Four patients were not evaluable for response. The response rate for the remaining 12 patients was 75% (7 complete responses and 2 partial responses). Six patients remained free of local failure until death (5 months and 7 months) or last follow-up (8 months, 11 months, 39 months, and 68 months). CONCLUSIONS: The current study indicates that combined reirradiation and hyperthermia for RAS in the thoracic region is feasible. The high response rate and the possibility of durable local control suggest that this treatment is promising.

Elective re-irradiation and hyperthermia following resection of persistent locoregional recurrent breast cancer: A retrospective study.

PURPOSE: To analyse the therapeutic effect and toxicity of re-irradiation (re-RT) combined with hyperthermia (HT) following resection or clinically complete remission (CR) of persistent locoregional recurrent breast cancer in previously irradiated area. METHODS AND MATERIALS: Between 1988 and 2001, 78 patients with high risk recurrent breast cancer underwent elective re-RT and HT. All patients received extensive previous treatments, including surgery and high-dose irradiation (> or =50Gy). Most had received one or more lines of systemic therapy; 44% had been treated for > or = one previous locoregional recurrences. At start of re-RT + HT there was no macroscopically detectable tumour following surgery (96%) or chemotherapy (CT). Re-RT typically consisted of eight fractions of 4Gy, given twice weekly. Hyperthermia was added once a week. RESULTS: After a median follow up of 64.2 months, three-year survival was 66%. Three- and five-year local control rates were 78% and 65%. Acute grade 3 toxicity occurred in 32% of patients. The risk of late > or = grade 3 toxicity was 40% after three years. Time interval to the current recurrence was found to be most predictive for local control in univariate and multivariate analysis. The extensiveness of current surgery was the most relevant treatment related factor associated with toxicity. CONCLUSIONS: For patients experiencing local recurrence in a previously radiated area, re-irradiation plus hyperthermia following minimisation of tumour burden leads to a high rate of local control, albeit with significant toxicity. The latter might be reduced by a more fractionated re-RT schedule.

Characteristics and performance evaluation of the capacitive Contact Flexible Microstrip Applicator operating at 70 MHz for external hyperthermia.

PURPOSE: To characterise and evaluate the capacitive Contact Flexible Microstrip Applicator operating at 70 MHz, CFMA-70. This applicator is introduced for the treatment of superficial tumours with extension in depth beyond the range of regular superficial applicators. METHODS: E-field measurements were performed in an elliptical phantom filled with a saline solution using an E-field vector probe. E-field distributions and SAR patterns are compared to those of the CFMA-434 and of 70 MHz waveguides. The applicator has been used for the treatment of 6 patients with breast cancer with a tumour depth exceeding 4 cm. RESULTS: The effective heating depth of the CFMA-70 is 50% larger than for the CFMA-434. Its effective field size is 26 x 20 cm (aperture 29 x 20 cm), larger than for an equally sized CFMA-434. In contrast to the CFMA-434 the SAR pattern of this applicator is insensitive to the bolus thickness. Comparison to 70 MHz waveguides shows that the E-field component normal to the applicator is 100% larger for the CFMA-70. During clinical applications acceptable temperatures were realised for individual sessions (also at depth), but in many cases treatment limiting hot spots occurred close to superficial bony structures near the applicator edge. Both surface irregularities and the normal field component may be responsible. CONCLUSIONS: The CFMA-70 has adequate penetration depth for the treatment of superficial tumours exceeding a depth of 4 cm. However, the relatively large normal E-field component may induce treatment-limiting hot spots at tissue interfaces in the direction normal to the applicator's surface.